Synthesis and characterization of 5-substituted 1,3-diazacyclohexane derivatives

Three synthetic routes to 5-substituted 1,3-diazacyclohexane derivatives 1 are reported. The first method involves treatment of 1, 3-diaminopropan-2-ol 2 with paraformaldehyde to yield 5-hydroxy-1, 3-diazacyclohexane 3. A second method is based on the condensation of 2-bromo-2-nitro-1,3-propanediol with tert-butylamine and formaldehyde to yield 1,3-di-tert-butyl-5-bromo-5-nitro-1, 3-diazacyclohexane 22. The third method relies on the cycloalkylation of methylenebisacetamide with 3-chloro-2-chloromethyl-2-propene to provide 5-exomethylene-1, 3-diacetyl-1,3-diazacyclohexane 28. Functional group manipulations of 3, 22, and 28 provide a number of novel 1,3-diazacyclohexanes functionalized at the 5-position.